article · Arabian Journal of Chemistry
Mohamed OuabaneComputational screening evaluated twenty-three pyrazole and pyrazoline derivatives to identify potential antimicrobial agents against Escherichia coli. Molecular docking and predictive absorption, distribution, metabolism, excretion, and toxicity analyses were conducted against a bacterial protein target. While all evaluated compounds displayed the ability to bind within the bacterial active site, four specific molecules designated as M6, M17, M19, and M20 showed particularly strong potential. These four candidates exhibited high binding affinity scores ranging from minus 9.3 to minus 10.3 kilocalories per mole and engaged key catalytic amino acid residues including Thr302, Thr300, Val270, and His298. Further evaluation against Lipinski rule of five criteria indicated that their physical and chemical profiles make them suitable candidates for orally active antibacterial drug development.
Bacterial infections such as those caused by Escherichia coli present persistent healthcare challenges, requiring a steady pipeline of candidate therapies. Using computer-based screening allows researchers to quickly identify promising chemical compounds and predict their safety and absorption profiles before starting expensive laboratory synthesis, accelerating the early search for effective new oral antibiotics.
This work identifies four early-stage lead compounds that could interest pharmaceutical and biotechnology companies developing small-molecule antibacterial treatments. Because the findings are based entirely on in silico docking and theoretical property screening, the candidates are at a very early discovery stage and will require chemical synthesis, laboratory binding validation, and in vitro antibacterial testing before any commercial development pathway can proceed.
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In the present study, a Molecular Docking and in silico ADMET analysis were performed to identify the possible inhibitory effect of 23 molecules, pyrazole and pyrazolines derivatives, on Escherichia coli and to predict the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of all compounds. According to the results, every compound examined might bind to this bacterium's active site (PDB: 1FJ4). The results obtained in silico demonstrated that Only 4 (M6, M17, M19 and M20) of the 23 compounds were selected due to their inhibitory action and proximity to the important catalytic residues Thr302, Thr300, Val270, and His298 of the major protease and could be considered as orally active drug candidates due to their physical and chemical properties. The compounds M6, M17, M19 and M20 were subjected to Lipinski’s rule of five because it has the best binding affinity score in the binding study of the compound with the protein (-9.6, -9.3, -9.5, -10.3 Kcal/mol) successively. Pyrazole derivatives and the structure of pyrazolines are also effectively discussed in this paper for potential application as antibacterial agents due to their significant inhibitory activity. We were also able to predict a new potential inhibitor against a target of interest because to the result that we obtained.
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DOI: 10.1016/j.arabjc.2023.105262
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